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Reversal of protein chemical aging by enzymatic deglycation

et al. used an innovative series of screening and directed evolution steps to produce a new enzyme (CMLase) which can remove a pernicious form of advanced glycation end product (AGE) linkage from proteins. AGEs contribute to biological aging, so CMLase may possess therapeutic potential to combat parts of the aging process.

Advanced glycation end products (AGEs) in proteins, a hallmark of aging, are considered irreversible. Here, authors report the development of CMLase — an enzyme that specifically oxidizes Nε-carboxymethyl-lysine (CML) and restores the native lysine residues in vitro and in human tissue samples.

DeepSeek’s new AI model is by far the cheapest of wellknown models to run, research firm says

A version of Chinese startup DeepSeek’s flagship AI model is by ‌far the least expensive to run on benchmark tests among well-known models globally and more than 100 times cheaper to run than Anthropic’s Claude Fable 5, according to a research firm.

Restoring Saliva Flow May Improve Oral Health in Down Syndrome

However, Carpenter was not entirely convinced that hyposalivation drives periodontitis. “I don’t think there’s much evidence for that in…literature about human studies,” he said. Instead, he said that inflammation—which is present in Dp16 salivary glands—could cause hyposalivation. “There’s lots of literature that shows that inflammatory cells can affect salivary secretion,” he noted.

According to Yule, next steps could include looking at whether dysregulated calcium signaling—which is linked with several other diseases—also underlies other Down syndrome-related complications like Alzheimer’s disease. While drugs targeting calcium signaling could potentially help, there is a complexity to it, he noted. “Knowing what the target is [is] good, but the fact that the target is almost universal in cells, then that makes you think about whether it’s something that could be targeted,” explained Yule.

Lacruz agreed that disrupted calcium signaling occurs in other tissues as well. “Understanding why calcium is dysregulated is an important part of what we need to do [next],” he said. More work needs to be done to translate the findings to the clinic, “but we see that as a way forward to potentially impacting the lives of individuals with Down syndrome,” said Lacruz.

Chronic Stress and Headaches: The Role of the HPA Axis and Autonomic Nervous System

Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased pain sensitivity, and vascular changes that could contribute to headache development and progression. The bidirectional nature of this relationship creates a vicious cycle, with recurrent headaches becoming a source of additional stress. Dysregulation of the HPA axis and ANS imbalance could amplify susceptibility to headaches, intensifying their frequency and severity. While pharmacological interventions remain common, non-pharmacological approaches targeting stress reduction, such as cognitive-behavioral therapy, biofeedback, and relaxation techniques, offer promising avenues for comprehensive headache management. By addressing the underlying stress-related mechanisms, these approaches provide a sustainable strategy to reduce headache frequency and improve patients’ quality of life.

JCI: Department of Immunology and Inflammation, Imperial College London, London, United Kingdom

2 School of Medicine, Chang Gung University and Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

3Imperial Lupus Centre, Imperial College Healthcare NHS Trust, London, United Kingdom.

Mouse study shows how liraglutide briefly rewires gut bacterial communities

Researchers treated male high-fat-fed mice with liraglutide for 14 days, then tracked fecal bacterial communities after a 7-day washout using 16S rRNA sequencing. Liraglutide shifted the microbiome toward Lactobacillus- and Leptogranulimonas-related taxa while reducing several fermentative taxa, but most changes moved back toward baseline after treatment stopped.

3D DNA mapping in rare immune cells reveals new genes linked with autoimmune disease risk

Our DNA is often pictured as a simple spiral, like a piece of rope held taut. But inside cells, it folds into a complex three-dimensional structure, with 2 meters (6.6 feet) of DNA scrunched like a headphone wire in a pocket. This bundled architecture plays a crucial role in how genes are switched on and off. Understanding these interactions is key to interpreting genetic studies of disease and can help develop targeted treatments.

Genes—the instructions for making proteins—are regulated by two types of DNA regions, called promoters and enhancers. Promoters are located at the start of each gene and directly load the machinery that reads it to produce RNA, a template for making proteins. In contrast, enhancers, which act like “molecular switches” boosting gene activity in the right cell and condition, may be found much further from the genes they control: sometimes many thousands or even millions of DNA letters away. When DNA folds in the 3D space of the cell’s nucleus, these enhancers loop around to physically contact the genes they regulate.

Understanding how enhancers work and which genes they control is particularly important because genome-wide association studies—large-scale efforts comparing the DNA of thousands of people to identify small genetic differences linked to disease—have revealed many genetic variants associated with complex conditions such as Crohn’s disease that sit within these regions. Crohn’s disease is a common form of inflammatory bowel disease, which affects around 1 in 100 people globally and currently has no known cure.

Abstract: Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA

2 Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

3Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.

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